Thong M K, Soo T L
Genetics Unit, Department of Paediatrics, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Singapore Med J. 2005 Jul;46(7):340-3.
Beta-thalassaemia major is one of the commonest genetic disorders in South East Asia. The strategy for the community control of beta-thalassaemia major requires the characterisation of the spectrum of beta-globin gene mutations in any multi-ethnic population. There is only a single report of mutation analyses of the beta-globin gene in an isolated Kadazandusun community in Kota Belud, Sabah, Malaysia, which showed the presence of a common 45 kb deletion.
To confirm the observation that this large deletion is the commonest beta-globin gene mutation among the Kadazandusun and other indigenous populations in Sabah, Malaysia, we performed polymerase chain reaction (PCR) analysis of the beta-globin gene in ten children with beta-thalassaemia major attending the Thalassaemia Centre, Queen Elizabeth Hospital, the major paediatric referral centre in Kota Kinabalu, Sabah.
The 45 kb deletion was confirmed to be the commonest mutation found in the Kadazandusun, Bajau and Murut populations, whereby it was detected in 19 out of the 20 (95 percent) alleles analysed. The other mutation was due to an IVS-1 position 1 G > T mutation.
This finding confirmed the deletion in the homozygous state was associated with a severe phenotype. The reason for the predominance of this mutation in Kota Kinabalu is most likely to be due to founder effects and possibly intermarriages between the various ethnic groups. Prenatal diagnosis using PCR for this common mutation is feasible in this community. Medical workers and scientists at molecular diagnostic centres serving large South East Asian populations should incorporate a diagnostic strategy for this deletion in the appropriate population. Future studies on these indigenous ethnic groups in other areas and other groups in Sabah are required.
重型β地中海贫血是东南亚最常见的遗传性疾病之一。对重型β地中海贫血进行社区控制的策略需要对任何多民族人群中的β珠蛋白基因突变谱进行特征分析。在马来西亚沙巴州哥打白洛一个与世隔绝的卡达山杜顺社区，仅有一份关于β珠蛋白基因突变分析的报告，该报告显示存在一种常见的45 kb缺失。
为了证实这一大型缺失是马来西亚沙巴州卡达山杜顺及其他原住民中最常见的β珠蛋白基因突变这一观察结果，我们对在哥打基纳巴卢主要儿科转诊中心伊丽莎白女王医院地中海贫血中心就诊的10名重型β地中海贫血患儿的β珠蛋白基因进行了聚合酶链反应（PCR）分析。
45 kb缺失被证实是在卡达山杜顺、巴夭和穆鲁特人群中发现的最常见突变，在所分析的20个等位基因中有19个（95%）检测到该突变。另一种突变是由于IVS-1第1位G>T突变。
这一发现证实纯合状态的缺失与严重表型相关。这种突变在哥打基纳巴卢占主导地位的原因很可能是奠基者效应以及不同种族之间可能的通婚。在这个社区，使用PCR对这种常见突变进行产前诊断是可行的。为东南亚大量人群服务的分子诊断中心的医务人员和科学家应在适当人群中纳入针对这种缺失的诊断策略。未来需要对其他地区的这些原住民群体以及沙巴的其他群体进行研究。
